Reactive oxidants modify essentially all biomolecules and nonradical electrophiles produced as byproducts of lipid oxidation also react with proteins. However, the reactions of electrophilic products of lipid peroxidation with most proteins have not been explored. New proteomics approaches based on tandem mass spectrometry (MS-MS) now enable the high-throughput characterization of protein adducts, mapping of modification sites and quantitation of adducts. The objective of this project is to characterize protein adduction by reactive lipid oxidation-derived electrophiles at the molecular level and to identify protein adducts in tissues and plasma as markers for oxidative stress. We hypothesize that specific protein adducts can both provide sensitive and chemically informative markers for oxidative stress in environmentally-related diseases. The